crossing96/oncoscreening huggingface dataset:
Epidemiology and genetic susceptibility to bladder cancer.	The incidence of bladder cancer varies considerably among countries; the highest incidence rates are in Western communities. The variation in occurrence can partly be explained by differences in registration and coding practices of pTa tumours. Factors that modify the occurrence of bladder cancer are smoking and exposure to many kinds of carcinogenic substances in the workplace. Evidence also exists for radiotherapy to the pelvis, infection with Schistosoma haematobium, and certain medications as risk factors for bladder cancer. Despite enormous efforts, other important environmental or lifestyle factors that clearly and consistently increase or decrease the risk of bladder cancer have not been identified. Bladder cancer in first-degree relatives doubles the risk of bladder cancer; this increased risk might be due to high-penetrance susceptibility genes in a small subset of families, but most of this risk is probably caused by common lower-penetrance DNA variants that influence risk through one or more different cancer pathways. In the next 2 years genome-wide association scans will probably yield important new information on such variants. This might also facilitate new studies on lifestyle factors restricted to groups of susceptible people. In the future it will also be necessary to pay more attention to potential risk factors for different types of bladder cancer, more specifically low- vs high-grade cancer. The ultimate goal is to build a risk-prediction model by integrating environmental and genetic factors that can project individualized probabilities of developing bladder cancer.	bladder
Shielding for scattered radiation to the testis during pelvic radiotherapy: is it worth?	OBJECTIVES: To assess the value of external shielding of the testis during pelvic radiotherapy. MATERIAL AND METHODS: Nineteen patients, receiving radiotherapy to the pelvis with the lower border of the field at the obturator foramen, were randomly selected. A 5 half value layer cerrobent shield was positioned at the inferior border of the field. The dose to the testis was measured with and without the shield. Observations were made regarding the reflex cremaster contraction and phantom measurements were done at different distances from the perineum. RESULTS: The mean radiation dose to the testis for patients receiving treatment with no shield was 7.4cGy (1.3) and it was 5.7cGy (-/+2.5) for patients with external shield, this difference was statistically significant by the paired t test p<0.0001. This accounted for a 22 % decrease in the dose received by the testis. The position of the testis with the contraction of the cremaster muscle and the dartos fascia after manipulation of the testis during diodes placement changed up to 3.5 cm (mean 1.5). Phantom measurements showed 37% increase in the dose with 2cm change in the position of the testis to the pelvic direction. CONCLUSION: External shield at the inferior border of the pelvic field is a simple, easy reproducible, convenient shielding method. Clam-shell scrotal shield is not free of drawbacks, but still its benefits overweigh its harms and should be used with caution.	bladder
p53 is localized to a sub-nucleolar compartment after proteasomal inhibition in an energy-dependent manner.	The tumor suppressor p53 is activated in response to many forms of cellular stress leading to cell cycle arrest, senescence or apoptosis. Appropriate sub-cellular localization is essential for modulating p53 function. We recently showed that p53 localizes to the nucleolus after proteasome inhibition with MG132 and this localization requires sequences within its carboxyl terminus. In the present study, we found that after treatment with MG132, p53 associates with a discrete sub-nucleolar component, the fibrillar center (FC), a region mainly enriched with RNA polymerase I. Moreover, we now demonstrate that this localization is an energy-dependent process as reduction of ATP levels prevents nucleolar localization. In addition, p53 sub-nucleolar accumulation is abolished when cells are subjected to various types of genotoxic stress. Furthermore, we show that monoubiquitination of p53, which causes it to localize to the cytoplasm and nucleoplasm, does not prevent the association of p53 with the nucleolus after MG132 treatment. Importantly, we demonstrate that p53 nucleolar association occurs in lung and bladder carcinomas.	bladder
Morphological and molecular profiles and pathways in bladder neoplasms.	After several decades of use of the Wealth Health Organization (WHO) 1973 grading system for bladder neoplasms (1973 WHO), a new grading system was adopted in 2004 by the WHO (2004 WHO). Some leading experts in the field of urogenital pathology have expressed their concerns with the 2004 WHO categorization system, both with regard to the nomenclature and the grading categories used. Several molecular and genetic studies have provided another perspective on the classification of urothelial neoplasms. The two most important developments are the identification of a mutation in the fibroblast growth factor receptor 3 gene in more than 50% of urothelial carcinomas and the discovery of cDNA profiles characteristic of different subsets of bladder cancer. There is strong correlation between the molecular findings and the 2004 WHO classification and prognosis.	bladder
EBAG9 is a tumor-promoting and prognostic factor for bladder cancer.	Upregulation of EBAG9 expression has been observed in several malignant tumors such as advanced breast and prostate cancers, indicating that EBAG9 may contribute to tumor proliferation. In the present study, we assess the role of EBAG9 in bladder cancer. We generated human bladder cancer EJ cells stably expressing FLAG-tagged EBAG9 (EJ-EBAG9) or empty vector (EJ-vector), and investigated whether EBAG9 overexpression modulates cell growth and migration in vitro as well as the in vivo tumor formation of EJ transfectants in xenograft models of BALB/c nude mice. EBAG9 overexpression promoted EJ cell migration, while the effect of EBAG9 to cultured cell growth was rather minimal. Tumorigenic experiments in nude mice showed that the size of EJ-EBAG9-derived tumors was significantly larger than EJ-vector-derived tumors. Loss-of-function study for EBAG9 using small interfering RNA (siRNA) in xenografts with parental EJ cells showed that the intra-tumoral injection of EBAG9 siRNA markedly reduced the EJ tumor formation compared with control siRNA. Furthermore, immunohistochemical study for EBAG9 expression was performed in 60 pathological bladder cancer specimens. Intense and diffuse cytoplasmic immunostaining was observed in 45% of the bladder cancer cases. Positive EBAG9 immunoreactivity was closely correlated with poor prognosis of the patients (p = 0.0001) and it was an independent prognostic predictor for disease-specific survival in multivariate analysis (p = 0.003). Our results indicate that EBAG9 would be a crucial regulator of tumor progression and a potential prognostic marker for bladder cancer.	bladder
Prognostic significance of nondiagnostic molecular changes in urine detected by UroVysion fluorescence in situ hybridization during surveillance for bladder cancer.	OBJECTIVES: To determine the outcomes for patients with nondiagnostic fluorescence in situ hybridization (FISH) (ie, < 4 gains of chromosomes 3, 7, or 17 in < or = 3 cells). FISH detects urothelial carcinoma and is especially beneficial in patients with negative or atypical urine cytology findings. A positive result is defined as a gain of > or = 2 chromosomes (3, 7, or 17) in 4 cells, isolated loss of 9p21 in 12 cells, or isolated gains of only 1 chromosome in > or = 10% of cells. Most FISH-positive patients will develop recurrent urothelial carcinoma within 1 year. METHODS: We compared the data from 149 patients with a nondiagnostic FISH result and > or = 30 months of follow-up with the data from patients with a negative FISH result from the same period. The time to conversion to a positive FISH result or the development of a bladder tumor was recorded. RESULTS: Patients with nondiagnostic FISH results had significantly greater rates of progression to positive FISH findings or the development of a bladder tumor than did patients with negative FISH findings. Most progression occurred within 1 year. Patients with nondiagnostic FISH results and concurrent negative cytology and cystoscopy had a very low risk of developing recurrent disease, similar to that found with truly negative FISH results. CONCLUSIONS: Nondiagnostic FISH results are related to a greater risk of progression to positive FISH results and tumor recurrence than those with negative FISH findings. However, after controlling for negative cytologic and cystoscopic status, a nondiagnostic FISH result does not appear to be an independent predictor of disease recurrence, and aggressive investigation is not warranted.	bladder
The impact of positive soft tissue surgical margins following radical cystectomy for high-grade, invasive bladder cancer.	INTRODUCTION: We evaluate the incidence and risk factors associated with positive soft tissue surgical margins (STSM) and determine the association with various surgical and pathological characteristics and clinical outcomes in patients undergoing radical cystectomy (RC) for bladder cancer. PATIENTS AND METHODS: From November 1971 to December 2005, 1,591 patients with primary transitional cell carcinoma (TCC) of the bladder underwent RC, with an extended bilateral pelvic lymphadenectomy and urinary diversion. A positive STSM was defined as tumor identified at the inked perivesical soft tissue surrounding the cystectomy specimen. Data were analyzed according to various clinical and pathologic variables, and survival analysis was performed. RESULTS: A total of 18 patients (1%) demonstrated pathologic evidence of a positive STSM following RC. Positive STSM were significantly associated with lymphovascular invasion, advanced pathologic stage, lymph node involvement, extent of nodal involvement and lymph node density. No patient with an organ-confined primary bladder tumor had a positive STSM, while 3% with extravesical tumor extension demonstrated a positive STSM. Recurrence-free and overall survival at 5 and 10 years for patients with a positive STSM was 29 and 22%, and 29 and 11%, respectively (p < 0.001). A positive STSM increased the risk of recurrence by threefold and the overall risk of death by 2.6 times. Only nine patients (1%) without evidence of nodal involvement had a positive STSM with a worse survival compared to those same pathologic subgroup and negative STSM. Nine patients (2%) with lymph node tumor involvement had positive STSM and also demonstrated significantly worse survival. CONCLUSION: Although a positive STSM was present in only 1% of patients undergoing a RC for TCC of the bladder, it was found to be an independent risk factor for advanced disease, lymph node involvement and tumor progression with worse survival. A dedicated effort should be made to avoid a positive STSM at the time of RC.	bladder
The role of lymph node density in bladder cancer prognostication.	Pelvic lymph node metastases from bladder cancer occur in about 25% of patients undergoing radical cystectomy. While the majority of patients with lymph node metastases will develop progressive disease, some patients do exhibit long-term survival with and without adjuvant chemotherapy. The concept of lymph node density has been proposed as a means to stratify patient prognosis since it takes into account two important factors-the number of positive nodes (tumor burden) and the total number of nodes removed/examined (extent of dissection). Due to the lack of agreement on the extent of lymphadenectomy, lymph node density facilitates standardization of lymph node staging, thus allowing for adjuvant therapies and clinical trials to be more uniformly applied. Whether lymph node density provides improved prognostication over the standard nodal staging or absolute number of positive lymph nodes remains controversial. We review the literature regarding the role of lymph node density in the prognostic stratification of node-positive bladder cancer.	bladder
[Therapeutic effect of mitomycin C in the immediate postoperatory in patients with low-risk non-muscle-invasive bladder tumours].	INTRODUCTION: Bladder cancer is a disease with a high prevalence due to its recurrence rate. Transurethral resection of the bladder (TURB) is the treatment in initial stages. Nevertheless, a high percentage of non-muscle-invasive tumors treated will have a recurrence 1-2 years afterwards. Adjuvant quemotherapy or immunotherapy after TURB has been administered in order to decrease the rate of recurrence and to prevent progression. PATIENTS AND METHODS: A prospectived, controlled and randomized study was performed. We included 100 patients with non-muscle-invasive and bladder tumors the low grade. All patients had initially a TURB performed and were randomized to either receive or not a single dose mitomycin C (MMC) in the immediate postoperatory. RESULTS: All low grade tumors was less than 3 cm. Mean follow-up was 26.43 +/- 7.65 months. MMC was administered in 49 patients, of these, 67.3% had no recurrence and 32.7% had a non-muscle-invasive recurrence. Of the 51 patients in the non mitomycin, 51% had no recurrence while 47% had a non-muscle-invasive recurrence, and 2% had a muscle-invasive progression. We found significantly differences in time to recurrence among the two groups. SUMMARY: We found a greater time to recurrence in the group of single dose adjuvant MMC being this difference statistically significantly when comparing with the other group.	bladder
Inhibition of pituitary tumors in Rb mutant chimeras through E2f4 loss reveals a key suppressive role for the pRB/E2F pathway in urothelium and ganglionic carcinogenesis.	The retinoblastoma protein pRB suppresses tumorigenesis largely through regulation of the E2F transcription factors. E2F4, the most abundant E2F protein, is thought to act in cooperation with pRB to restrain cell proliferation. In this study, we analyse how loss of E2f4 affects the tumorigenicity of pRB-deficient tissues. As Rb(-/-);E2f4(-/-) germline mice die in utero, we generated Rb(-/-);E2f4(-/-) chimeric animals to allow examination of adult tumor phenotypes. We found that loss of E2f4 had a differential effect on known Rb-associated neuroendocrine tumors. It did not affect thyroid and adrenal glands tumors but partially suppressed lung neuroendocrine hyperplasia. The most striking effect was in the pituitary where E2F4 loss delayed the development, and reduced the incidence, of Rb mutant tumors. This tumor suppression increased the longevity of the Rb(-/-);E2f4(-/-) chimeric animals allowing us to identify novel tumor types. We observed ganglionic neuroendocrine neoplasms, lesions not associated earlier with mutation of either Rb or E2f4. Moreover, a subset of the Rb(-/-);E2f4(-/-) chimeras developed either low- or high-grade carcinomas in the urothelium transitional epithelium supporting a key role for Rb in bladder cancer.	bladder
Arsenic and bladder cancer: observations and suggestions.	Arsenic from drinking water is a well-known risk factor for bladder cancer. The purpose of this paper is to systematize some important yet often overlooked facts considering the relationship between arsenic exposure and the occurrence of bladder cancer. Since the exposure to inorganic arsenic from food, inhaled air, and skin absorption as well as arsenic methylation ability are not fully investigated, our assumption is that the exposure of arsenic only from drinking water is underestimated and its role as a risk factor is highly overestimated. This paper proposes some qualitative and quantitative parameters of arsenic as a risk factor for bladder cancer. The recommended qualitative parameters of arsenic intake are first, pathways of exposure, and second, toxicity and metabolism. The suggested quantitative parameters of arsenic intake include amounts of arsenic absorbed in the body, duration of arsenic exposure, and duration of arsenic presence in the urinary bladder. This approach can be implemented in a systematic classification and explanation of various risk factors and their mutual interactions for other types of cancer or diseases in general.	bladder
A technique for resection of invasive tumors involving the trigone area of the bladder in dogs: preliminary results in two dogs.	OBJECTIVE: To describe a surgical technique for resection of the entire bladder neck, including the trigone and proximal urethra in dogs with invasive tumors causing life-threatening urinary tract obstruction. STUDY DESIGN: Clinical case reports. ANIMALS: Dogs (n=2) with bladder tumors. METHODS: Circumferential excision of the bladder neck and proximal urethra with preservation of the neurovascular pedicles was performed to remove a rhabdomyosarcoma (dog 1) and a transitional cell carcinoma (dog 2) involving the trigone and bladder neck that were causing urinary tract obstruction. Reconstruction of the bladder and proximal urethra included bilateral ureteroneocystostomy. Adjuvant chemotherapy was administered postoperatively to both dogs. RESULTS: Postoperatively, dogs 1 and 2 were continent after 7 and 17 days, respectively, and regained normal urinary function after resolution of a transient pollakiuria. Dog 1 had no evidence of local or regional recurrence; however, a large solitary pulmonary metastatic lesion was diagnosed 8 months later. The dog was euthanatized despite a lack of clinical signs. Dog 2 had at least 1 metastatic lesion in the abdominal wall 6 months later and was euthanatized at 580 days because of renal failure. CONCLUSION: En-bloc removal of the bladder neck and proximal urethra with preservation of the dorsal vascular and nervous pedicles, although a technically challenging procedure, can be performed without associated urinary incontinence or bladder wall necrosis. CLINICAL RELEVANCE: In dogs with invasive bladder tumors causing life-threatening urinary tract obstruction, resection of the bladder neck and proximal urethra should be considered as a promising surgical alternative to urinary diversion.	bladder
Expression parameters of the polycomb group proteins BMI1, SUZ12, RING1 and CBX7 in urothelial carcinoma of the bladder and their prognostic relevance.	BACKGROUND: The polycomb group (PCG) proteins are epigenetic transcriptional repressors involved in the control of cellular proliferation and oncogenesis. This study aimed at examining whether mRNA tumor levels of the PCG family members BMI1, SUZ12, RING1, and CBX7 relate to histopathological parameters in urothelial carcinomas of the bladder and whether they may provide prognostic information following tumor resection. METHODS: The relative gene expression of BMI1, SUZ12, RING1, and CBX7 was analyzed by real-time RT-PCR in tumor tissue obtained from 93 patients with urothelial carcinoma of the bladder undergoing surgical treatment. Expression data was correlated with pathological variables and outcome. RESULTS: PCG family members BMI1, SUZ12, RING1, and CBX7 are commonly expressed in urothelial carcinomas of the bladder. The relative CBX7 mRNA expression levels gradually decreased from superficial (pTa) to invasive (pT1) and finally to muscle-invasive (> or =pT2) tumors (p = 0.008). Furthermore, CBX7 expression was statistically significantly correlated with tumor grade (p = 0.04). No correlation of mRNA levels with histopathological tumor features or tumor recurrence was observed for the other PCG components investigated. CONCLUSION: Expression levels of CBX7 inversely correlate with the progression of tumor stage and grade in urothelial carcinomas of the bladder, suggesting that downregulation of CBX7 indicates aggressive urothelial carcinoma phenotype.	bladder
Chromosomal aberrations in urothelial carcinoma of the bladder and the World Health Organization 2004 grading system.	OBJECTIVE: To evaluate differences in chromosomal aberrations in recurrent urothelial cancer (UC) of the bladder between the World Health Organization (WHO) 1973 and 2004 classification a retrospective study was performed. STUDY DESIGN: Primary and recurrent UCs of the bladder of 22 patients diagnosed at the Institute of Pathology, Medical University of Innsbruck were analyzed by comparative genomic hybridization, fluorescence in situ hybridization and immunohistochemistry (Ki-67, p53). RESULTS: On average, there were 5.8 +/- 5.9 alterations, including 4.1 +/- 4.3 gains and 3.5 +/- 2.5 losses per tumor. Most frequent gains ofchromosomal material were found on 19p, 7q, 16, 19q, 89, 12q and 20. Most frequent losses of chromosomal material were detected on 9, 13q, 5q, 8p, 11p and 18q. Total number of aberrations differed significantly between tumor grades of WHO 1973 and 2004 grading systems (p = 0.020 and p = 0.028). Chromosomal aberrations correlated well with both grading systems. Grade 2 tumors, reclassified as high-grade tumors, were of higher stage and showed aberrations usually associated with higher grade and poor outcome (1p+, 16p+, -2 and -5q). CONCLUSION: Our findings suggest that G2 tumors form a heterogeneous group supporting the value of the new WHO 2004 classification.	bladder
Combined-modality therapy with gemcitabine and radiation therapy as a bladder preservation strategy: long-term results of a phase I trial.	PURPOSE: A Phase I trial of twice-weekly gemcitabine and concurrent radiation therapy (RT) was performed in patients with muscle-invasive bladder cancer. We present the final analysis of bladder-intact survival (BIS), disease-specific survival (DSS), and overall survival (OS). METHODS AND MATERIALS: Eligible patients had muscle-invasive transitional cell carcinoma (cT2-3) and were candidates for cystectomy. Patients underwent maximal transurethral resection of bladder tumor followed by twice-weekly gemcitabine with concurrent RT to the bladder (total of 60 Gy over 6 weeks). Gemcitabine doses ranged from 10 to 33 mg/m(2). RESULTS: Median follow-up was 5.6 years (range, 0.6-9.5 years). Twenty-three of 24 patients were evaluable for response. All patients were clinical stage T2. Locoregional failure occurred in seven patients (30%), which were successfully salvaged by radical cystectomy (n = 5) or intravesical therapy (n = 2). Four local failures occurred > 5 years after therapy. Most local failures were noninvasive tumors (Ta or Tis, n = 6). Ten patients (43%) experienced optimal outcome (no failures and bladder intact). The 5-year actuarial estimates of survival are BIS 62%, OS 76%, and DSS 82%. CONCLUSION: Twice-weekly gemcitabine with concurrent RT is well tolerated and provides rates of survival and bladder preservation that are comparable to the existing literature. All locoregional failures were successfully salvaged by either radical cystectomy or intravesical therapy. Given the high proportion of late local failures, we recommend long-term monitoring when using this regimen. Future studies comparing the safety and efficacy of gemcitabine- vs. platinum-based bladder preservation protocols are pending.	bladder